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Bioavailability of propranolol in the dog

F L Tse, T M Sanders, J P Reo

    Archives Internationales De Pharmacodynamie Et De Therapie
    |December 1, 1980
    PubMed
    Summary

    This study investigated propranolol pharmacokinetics in dogs, revealing significant tissue uptake and a prolonged biological half-life after oral and intraportal administration. Oral bioavailability was found to be 27% due to extensive first-pass metabolism.

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    Area of Science:

    • Pharmacology
    • Veterinary Medicine
    • Drug Metabolism

    Background:

    • Propranolol is a widely used beta-blocker with established therapeutic applications.
    • Understanding its pharmacokinetic profile is crucial for optimizing dosing and predicting therapeutic outcomes.
    • Species-specific differences in drug metabolism necessitate pharmacokinetic evaluations in relevant animal models.

    Purpose of the Study:

    • To characterize the pharmacokinetics of propranolol in fasted dogs.
    • To compare propranolol absorption, distribution, metabolism, and excretion (ADME) following intravenous, intraportal, and oral administration.
    • To determine the extent of first-pass metabolism and overall oral bioavailability of propranolol.

    Main Methods:

    • Single oral, intraportal, and intravenous doses of propranolol were administered to fasted dogs.
    • Plasma and tissue concentrations of propranolol were measured over time.
    • Pharmacokinetic parameters including distribution volume, biological half-life, absorption efficiency, and bioavailability were calculated.

    Main Results:

    • Extensive tissue uptake of propranolol was observed after intravenous dosing, with a distribution volume of 11 L/kg.
    • The biological half-life of propranolol was 1.5 hours but was prolonged following oral and intraportal administration.
    • Oral absorption efficiency of unchanged propranolol was 71%, with 62% loss due to first-pass metabolism, resulting in 27% oral bioavailability.

    Conclusions:

    • Propranolol undergoes significant first-pass metabolism in dogs, substantially reducing its oral bioavailability.
    • The pharmacokinetic profile suggests extensive tissue distribution and a relatively short biological half-life in this species.
    • These findings are critical for understanding propranolol's disposition in dogs and informing potential therapeutic use.

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